RESUMO
Genistein is a phytoestrogen that is known to have a protective effect on the vascular endothelial wall. However, it exhibits poor bioavailability, which limits the use of genistein to treat cardiovascular and cerebrovascular diseases. A novel genistein derivative, 7-difluoromethyl-5,4'-dimethoxygenistein (dFMGEN), has shown a better protective effect on vascular endothelial damage in vitro than genistein. In this study, we further evaluated therapeutic effects of dFMGEN on the vascular endothelial wall and atherosclerosis in a rabbit model in vivo. There were 5 groups: the GEN group (genistein 5 mg/kg per day), lovastatin group (lovastatin 5 mg/kg per day), dFMGEN group (dFMGEN 5 mg/kg per day), model control group (the same amount of vehicle solvent), and the normal control group; all feedings administered via intragastric administration. We demonstrated that dFMGEN (1) attenuated the development of atherosclerosis, (2) reduced serum total cholesterol and low-density lipoprotein cholesterol concentrations, (3) decreased lipid peroxidation in the rabbit atherosclerosis model, and (4) increased smooth muscle cell and collagen content in atheroma of thoracic aortas. These results provide an experimental foundation for dFMGEN's potential effects in preventing and treating atherosclerosis, acute coronary syndromes, and potentially ischemia-reperfusion injury during acute myocardial infarction and cerebral infarction.
Assuntos
Aterosclerose/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Genisteína/análogos & derivados , Fitoestrógenos/uso terapêutico , Animais , Aorta Abdominal/efeitos dos fármacos , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Aterosclerose/sangue , Aterosclerose/metabolismo , Aterosclerose/patologia , Colesterol/sangue , Colágeno/metabolismo , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Genisteína/administração & dosagem , Genisteína/uso terapêutico , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoproteínas LDL/sangue , Masculino , Fitoestrógenos/administração & dosagem , CoelhosRESUMO
OBJECTIVE: To study the effect of differentiation of HL-60 cells by induction of SPGL. METHODS: Cell differentiation was analyzed by using Wrigh-Giemsa staining to observe the morphology changes of cells with microscope, NBT reductant test, surface differentiation antigen (CD11b and CD14) test in HL-60 cells treated by different doses (1 x 10(-5) - 5 x 10(-4) ng/ml) of SPGL at the 3th day. RESULTS: The morphological changes showed cell differentiation characteristics; NBT reductant was significantly increased, and the number of NBT positive cells were related to dose of SPGL (in dose-dependent manner); Expression of CD11b and CD14 increased obviously. CONCLUSION: The results indicate that the effect of differentiation of HL-60 cells by induction of SPGL and it induces the cells to differentiate along the monocyte and granulocyte lineage.